Based on a study of molecular pathways involved in tumour growth, a number of potential anti-angiogenic agents have been identified. Bevazicumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), has been studied in the first-line treatment of ovarian cancer.73
The ICON7, a phase III randomised study, compared standard chemotherapy (carboplatin AUC 5 or 6 and paclitaxel 175 mg/m2 every 3 weeks for 6 cycles) or standard chemotherapy plus bevacizumab (7.5 mg per kilo body weight) given concurrently every 3 weeks for 5 or 6 cycles and continued for 12 additional cycles or until progression of disease.14
GOG 218, a double-blind phase III randomised controlled trial compared three treatments. Each of the three study regimens comprised 22 3-week cycles paclitaxel 175 mg/m2 plus carboplatin AUC 6. Control treatment was chemotherapy with placebo added in cycles 2 through 22; bevacizumab initiation treatment was chemotherapy with bevacizumab (15 mg per kg body weight) added in cycles 2 through 6 and placebo added in cycles 7 through 22. Bevacizumab-throughout treatment was chemotherapy with bevacizumab added in cycles 2 through 22. 15
Overall survival
The ICON7 trial reported that there were no overall survival differences between treatment groups. However, improved survival was reported in a subgroup of patients (n=465) at high risk of progression (stage IV disease or stage III and >1 cm residual disease) in the bevacizumab (7.5 mg/kg body weight) plus standard therapy (carboplatin + paclitaxel) group, compared to the standard therapy alone group.14 Patients in the bevacizumab arm had improved survival OS median 36.6 months in intervention group, 28.8 months in control group, HR 0.64 (95% CI 0.48 to 0.85), p=0.002.14
In the GOG 218 trial, bevacizumab (15 mg/kg body weight) was given every three weeks, in addition to the standard carboplatin/paclitaxel regimen. No significant differences in overall survival were reported between the three groups (bezacizumab-initiation group, bezacizumab-throughout group and control group).15
Progression-free survival
In the updated analyses from ICON7, improved progression-free survival, (19.8 months vs. 17.4 months; p=0.04), was reported in the group receiving bevazicumab (7.5 mg/kg of body weight), compared with standard therapy.14 The maximum improvement was at 12 months, co-inciding with the end of planned bevacizumab treatment, and diminished by 24 months. Median PFS in the updated analyses was 16 months in the bevacizumab group compared with 10.5 months in the standard therapy group (p=0.002).14
In GOG2018, progression-free survival was improved in the bevacizumab throughout arm (median 14.1 months) compared with control (median 10.3 months) (p<0.001), however this improvement was not observed in the bevacizumab initiation arm (median 11.2 months) (p=0.16).15
Adverse events
In GOG 218, in both arms concurrent bevacizumab compared to control group without bevacizumab, doubled the odds of a gastrointestinal adverse event (odds ratio 2.15, 95% CI 1.05-4.40, p=0.032), after controlling for history of treatment for irritable bowel disease, small bowel resection at primary surgery and bowel resection at primary surgery, however was not appreciably increased by continuation of bevacizumab beyond chemotherapy.55
Quality of life
In ICON7, bevacizumab treatment was associated with a small but clinically significant decrease in quality of life compared to standard chemotherapy.54